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The dysfunction of hormone-sensitive lipase induces lipid deposition and reprogramming of nutrient metabolism in fish
Published online by Cambridge University Press: 21 November 2022
Abstract
Hormone-sensitive lipase (HSL) is one of the rate-determining enzymes in the hydrolysis of TAG, playing a crucial role in lipid metabolism. However, the role of HSL-mediated lipolysis in systemic nutrient homoeostasis has not been intensively understood. Therefore, we used CRISPR/Cas9 technique and Hsl inhibitor (HSL-IN-1) to establish hsla-deficient (hsla-/-) and Hsl-inhibited zebrafish models, respectively. As a result, the hsla-/- zebrafish showed retarded growth and reduced oxygen consumption rate, accompanied with higher mRNA expression of the genes related to inflammation and apoptosis in liver and muscle. Furthermore, hsla-/- and HSL-IN-1-treated zebrafish both exhibited severe fat deposition, whereas their expressions of the genes related to lipolysis and fatty acid oxidation were markedly reduced. The TLC results also showed that the dysfunction of Hsl changed the whole-body lipid profile, including increasing the content of TG and decreasing the proportion of phospholipids. In addition, the systemic metabolic pattern was remodelled in hsla-/- and HSL-IN-1-treated zebrafish. The dysfunction of Hsl lowered the glycogen content in liver and muscle and enhanced the utilisation of glucose plus the expressions of glucose transporter and glycolysis genes. Besides, the whole-body protein content had significantly decreased in the hsla-/- and HSL-IN-1-treated zebrafish, accompanied with the lower activation of the mTOR pathway and enhanced protein and amino acid catabolism. Taken together, Hsl plays an essential role in energy homoeostasis, and its dysfunction would cause the disturbance of lipid catabolism but enhanced breakdown of glycogen and protein for energy compensation.
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- © The Author(s), 2022. Published by Cambridge University Press on behalf of The Nutrition Society
References
Peirce, V, Carobbio, S & Vidal-Puig, A (2014) The different shades of fat. Nature 510, 76–83.CrossRefGoogle ScholarPubMed
Cerk, IK, Wechselberger, L & Oberer, M (2017) Adipose triglyceride lipase regulation: an overview. Curr Protein Pept Sci 19, 221–233.CrossRefGoogle Scholar
Arner, P & Langin, D (2014) Lipolysis in lipid turnover, cancer cachexia, and obesity-induced insulin resistance. Trends Endocrinol Metab 25, 255–262.CrossRefGoogle ScholarPubMed
Zechner, R, Zimmermann, R, Eichmann, TO, et al. (2012) FAT SIGNALS--lipases and lipolysis in lipid metabolism and signaling. Cell Metab 15, 279–291.CrossRefGoogle ScholarPubMed
Montagner, A, Polizzi, A, Fouché, E, et al. (2016) Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD. Gut 65, 1202–1214.CrossRefGoogle ScholarPubMed
Schweiger, M, Schreiber, R, Haemmerle, G, et al. (2006) Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism. J Biol Chem 281, 40236–40241.CrossRefGoogle ScholarPubMed
Lafontan, M & Langin, D (2009) Lipolysis and lipid mobilization in human adipose tissue. Prog Lipid Res 48, 275–297.CrossRefGoogle ScholarPubMed
Recazens, E, Mouisel, E & Langin, D (2021) Hormone-sensitive lipase: sixty years later. Prog Lipid Res 82, 101084.CrossRefGoogle ScholarPubMed
Haemmerle, G, Moustafa, T, Woelkart, G, et al. (2011) ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPAR-α and PGC-1. Nat Med 17, 1076–1085.CrossRefGoogle ScholarPubMed
Granneman, JG, Moore, HP, Krishnamoorthy, R, et al. (2009) Perilipin controls lipolysis by regulating the interactions of AB-hydrolase containing 5 (Abhd5) and adipose triglyceride lipase (Atgl). J Biol Chem 284, 34538–34544.CrossRefGoogle ScholarPubMed
Gaidhu, MP, Anthony, NM, Patel, P, et al. (2010) Dysregulation of lipolysis and lipid metabolism in visceral and subcutaneous adipocytes by high-fat diet: role of ATGL, HSL, and AMPK. Am J Physiol Cell Physiol 298, C961–971.CrossRefGoogle ScholarPubMed
Harada, K, Shen, WJ, Patel, S, et al. (2003) Resistance to high-fat diet-induced obesity and altered expression of adipose-specific genes in HSL-deficient mice. Am J Physiol Endocrinol Metab 285, E1182–1195.CrossRefGoogle ScholarPubMed
Lampidonis, AD, Rogdakis, E, Voutsinas, GE, et al. (2011) The resurgence of Hormone-Sensitive Lipase (HSL) in mammalian lipolysis. Gene 477, 1–11.CrossRefGoogle ScholarPubMed
Scalvini, L, Piomelli, D & Mor, M (2016) Monoglyceride lipase: structure and inhibitors. Chem Phys Lipids 197, 13–24.CrossRefGoogle ScholarPubMed
Garton, AJ, Campbell, DG, Cohen, P, et al. (1988) Primary structure of the site on bovine hormone-sensitive lipase phosphorylated by cyclic AMP-dependent protein kinase. FEBS Lett 229, 68–72.CrossRefGoogle ScholarPubMed
Tsiloulis, T & Watt, MJ (2015) Exercise and the regulation of adipose tissue metabolism. Prog Mol Biol Transl Sci 135, 175–201.CrossRefGoogle ScholarPubMed
Kim, BY, Yoo, W, Huong Luu Le, LT, et al. (2019) Characterization and mutation anaylsis of a cold-active bacterial hormone-sensitive lipase from Salinisphaera sp. P7–4. Arch Biochem Biophys 663, 132–142.CrossRefGoogle ScholarPubMed
Krintel, C, Osmark, P, Larsen, MR, et al. (2008) Ser649 and Ser650 are the major determinants of protein kinase A-mediated activation of human hormone-sensitive lipase against lipid substrates. PLoS One 3, e3756.CrossRefGoogle ScholarPubMed
Albert, JS, Yerges-Armstrong, LM, Horenstein, RB, et al. (2014) Null mutation in hormone-sensitive lipase gene and risk of type 2 diabetes. N Engl J Med 370, 2307–2315.CrossRefGoogle ScholarPubMed
Mulder, H, Sorhede-Winzell, M, Contreras, JA, et al. (2003) Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact. J Biol Chem 278, 36380–36388.CrossRefGoogle ScholarPubMed
Roduit, R, Masiello, P, Wang, SP, et al. (2001) A role for hormone-sensitive lipase in glucose-stimulated insulin secretion: a study in hormone-sensitive lipase-deficient mice. Diabetes 50, 1970–1975.CrossRefGoogle ScholarPubMed
Xia, B, Cai, GH, Yang, H, et al. (2017) Adipose tissue deficiency of hormone-sensitive lipase causes fatty liver in mice. PLos Genet 13, e1007110.CrossRefGoogle ScholarPubMed
Wang, SP, Laurin, N, Himms-Hagen, J, et al. (2001) The adipose tissue phenotype of hormone-sensitive lipase deficiency in mice. Obes Res 9, 119–128.CrossRefGoogle ScholarPubMed
Haemmerle, G, Zimmermann, R, Hayn, M, et al. (2002) Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J Biol Chem 277, 4806–4815.CrossRefGoogle ScholarPubMed
Marshall, S (2006) Role of insulin, adipocyte hormones, and nutrient-sensing pathways in regulating fuel metabolism and energy homeostasis: a nutritional perspective of diabetes, obesity, and cancer. Sci STKE 2006, re7.CrossRefGoogle ScholarPubMed
Walker, C, Sugden, M, Gibbons, G, et al. (2007) Peroxisome proliferator-activated receptor α deficiency modifies glucose handling by isolated mouse adipocytes. J Endocrinol 193, 39–43.CrossRefGoogle ScholarPubMed
Burri, L, Thoresen, GH & Berge, RK (2010) The role of PPAR activation in liver and muscle. PPAR Res 2010, 542359.CrossRefGoogle ScholarPubMed
Cha, DR, Han, JY, Su, DM, et al. (2007) Peroxisome proliferator-activated receptor-
α
deficiency protects aged mice from insulin resistance induced by high-fat diet. Am J Nephrol 27, 479–482.CrossRefGoogle ScholarPubMed
Desai, A, Singh, R, Sapkale, P, et al. (2010) Effects of feed supplementation with L-carnitine on growth and body composition of Asian catfish, Clarias batrachus fry. J Appl Anim Res 38, 153–157.CrossRefGoogle Scholar
Li, L-Y, Li, J-M, Ning, L-J, et al. (2020) Mitochondrial fatty acid β-oxidation inhibition promotes glucose utilization and protein deposition through energy homeostasis remodeling in fish. J Nutr 150, 2322–2335.CrossRefGoogle ScholarPubMed
Morigny, P, Houssier, M, Mouisel, E, et al. (2016) Adipocyte lipolysis and insulin resistance. Biochimie 125, 259–266.CrossRefGoogle ScholarPubMed
Den Broeder, MJ, Kopylova, VA, Kamminga, LM, et al. (2015) Zebrafish as a model to study the role of peroxisome proliferating-activated receptors in adipogenesis and obesity. PPAR Res 2015, 358029.CrossRefGoogle Scholar
Lu, DL, Ma, Q, Wang, J, et al. (2019) Fasting enhances cold resistance in fish through stimulating lipid catabolism and autophagy. J Physiol 597, 1585–1603.CrossRefGoogle ScholarPubMed
Naser, FJ, Jackstadt, MM, Fowle-Grider, R, et al. (2021) Isotope tracing in adult zebrafish reveals alanine cycling between melanoma and liver. Cell Metab 33, 1493–1504.e1495.CrossRefGoogle ScholarPubMed
Quinlivan, VH & Farber, SA (2017) Lipid uptake, metabolism, and transport in the larval zebrafish. Front Endocrinol 8, 319.CrossRefGoogle ScholarPubMed
Li, L-Y, Lu, D-L, Jiang, Z-Y, et al. (2020) Dietary L-carnitine improves glycogen and protein accumulation in Nile tilapia via increasing lipid-sourced energy supply: an isotope-based metabolic tracking. Aquacult Rep 17, 100302.Google Scholar
Yan, J, Liao, K, Wang, T, et al. (2015) Dietary lipid levels influence lipid deposition in the liver of large yellow croaker (Larimichthys crocea) by regulating lipoprotein receptors, fatty acid uptake and triacylglycerol synthesis and catabolism at the transcriptional level. PLoS One 10, e0129937.CrossRefGoogle ScholarPubMed
Liu, D, Mai, K & Ai, Q (2015) Tumor necrosis factorα is a potent regulator in fish adipose tissue. Aquacult 436, 65–71.CrossRefGoogle Scholar
Chen, QL, Luo, Z, Song, YF, et al. (2014) Hormone-sensitive lipase in yellow catfish Pelteobagrus fulvidraco: molecular characterization, mRNA tissue expression and transcriptional regulation by leptin in vivo and in vitro
. Gen Comp Endocrinol 206, 130–138.CrossRefGoogle ScholarPubMed
Sun, J, Ji, H, Li, XX, et al. (2016) Lipolytic enzymes involving lipolysis in Teleost: synteny, structure, tissue distribution, and expression in grass carp (Ctenopharyngodon idella). Comp Biochem Physiol B: Biochem Mol Biol 198, 110–118.CrossRefGoogle ScholarPubMed
Cruz-Garcia, L, Sanchez-Gurmaches, J, Bouraoui, L, et al. (2011) Changes in adipocyte cell size, gene expression of lipid metabolism markers, and lipolytic responses induced by dietary fish oil replacement in gilthead sea bream (Sparus aurata L.). Comp Biochem Physiol A Mol Integr Physiol 158, 391–399.CrossRefGoogle ScholarPubMed
Hu, Y, Huang, Y, Tang, T, et al. (2020) Effect of partial black soldier fly (Hermetia illucens L.) larvae meal replacement of fish meal in practical diets on the growth, digestive enzyme and related gene expression for rice field eel (Monopterus albus). Aquacult Rep 17, 100345.Google Scholar
Jin, M, Pan, T, Tocher, DR, et al. (2019) Dietary choline supplementation attenuated high-fat diet-induced inflammation through regulation of lipid metabolism and suppression of NFkappaB activation in juvenile black seabream (Acanthopagrus schlegelii). J Nutr Sci 8, e38.CrossRefGoogle ScholarPubMed
Jin, M, Lu, Y, Yuan, Y, et al. (2017) Regulation of growth, antioxidant capacity, fatty acid profiles, hematological characteristics and expression of lipid related genes by different dietary n-3 highly unsaturated fatty acids in juvenile black seabream (Acanthopagrus schlegelii). Aquacult 471, 55–65.CrossRefGoogle Scholar
Han, SL, Qian, YC, Limbu, SM, et al. (2021) Lipolysis and lipophagy play individual and interactive roles in regulating triacylglycerol and cholesterol homeostasis and mitochondrial form in zebrafish. Biochim Biophys Acta, Mol Cell Biol Lipids 1866, 158988.CrossRefGoogle ScholarPubMed
Han, SL, Liu, Y, Limbu, SM, et al. (2021) The reduction of lipid-sourced energy production caused by ATGL inhibition cannot be compensated by activation of HSL, autophagy, and utilization of other nutrients in fish. Fish Physiol Biochem 47, 173–188.CrossRefGoogle ScholarPubMed
Li, LY, Limbu, SM, Ma, Q, et al. (2018) The metabolic regulation of dietary L-carnitine in aquaculture nutrition: present status and future research strategies. Rev Aquacult 11, 1228–1257.CrossRefGoogle Scholar
Abo Alrob, O & Lopaschuk, GD (2014) Role of CoA and acetyl-CoA in regulating cardiac fatty acid and glucose oxidation. Biochem Soc Trans 42, 1043–1051.CrossRefGoogle ScholarPubMed
Han, S-L, Wang, J, Li, L-Y, et al. (2020) The regulation of rapamycin on nutrient metabolism in Nile tilapia fed with high-energy diet. Aquacult 520, 734975.CrossRefGoogle Scholar
Karpac, J & Jasper, HJC (2011) Metabolic homeostasis: HDACs take center stage. Cell 145, 497–499.CrossRefGoogle ScholarPubMed
Rose, S, Frye, RE, Slattery, J, et al. (2014) Oxidative stress induces mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines in a well-matched case control cohort. PLoS One 9, e85436.CrossRefGoogle Scholar
Horikoshi, Y, Yan, Y, Terashvili, M, et al. (2019) Fatty acid-treated induced pluripotent stem cell-derived human cardiomyocytes exhibit adult cardiomyocyte-like energy metabolism phenotypes. Cells 8, 1095.CrossRefGoogle ScholarPubMed
Pajed, L, Taschler, U, Tilp, A, et al. (2021) Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase. Commun Biol 4, 1–13.CrossRefGoogle ScholarPubMed
Haemmerle, G, Lass, A, Zimmermann, R, et al. (2006) Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 312, 734–737.CrossRefGoogle ScholarPubMed
Fischer, J, Lefevre, C, Morava, E, et al. (2007) The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy. Nat Genet 39, 28–30.CrossRefGoogle ScholarPubMed
Park, SY, Kim, HJ, Wang, S, et al. (2005) Hormone-sensitive lipase knockout mice have increased hepatic insulin sensitivity and are protected from short-term diet-induced insulin resistance in skeletal muscle and heart. Am J Physiol Endocrinol Metab 289, E30–E39.CrossRefGoogle ScholarPubMed
Voshol, PJ, Haemmerle, G, Ouwens, DM, et al. (2003) Increased hepatic insulin sensitivity together with decreased hepatic triglyceride stores in hormone-sensitive lipase-deficient mice. Endocrinology 144, 3456–3462.CrossRefGoogle ScholarPubMed
Girousse, A, Tavernier, G, Valle, C, et al. (2013) Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass. PLoS Biol 11, e1001485.CrossRefGoogle ScholarPubMed
Morigny, P, Houssier, M, Mairal, A, et al. (2019) Interaction between hormone-sensitive lipase and ChREBP in fat cells controls insulin sensitivity. Nat Metab 1, 133–146.CrossRefGoogle ScholarPubMed
Inoki, K, Corradetti, MN & Guan, KL (2005) Dysregulation of the TSC-mTOR pathway in human disease. Nat Genet 37, 19–24.CrossRefGoogle ScholarPubMed
Wang, X & Proud, CG (2006) The mTOR pathway in the control of protein synthesis. Physiology 21, 362–369.CrossRefGoogle ScholarPubMed
Targher, G, Bertolini, L, Scala, L, et al. (2005) Non-alcoholic hepatic steatosis and its relation to increased plasma biomarkers of inflammation and endothelial dysfunction in non-diabetic men. Role of visceral adipose tissue. Diabetic Med 22, 1354–1358.CrossRefGoogle Scholar
Hijona, E, Hijona, L, Arenas, JI, et al. (2010) Inflammatory mediators of hepatic steatosis. Mediat Inflamm 2010, 837419.CrossRefGoogle ScholarPubMed
Cheng, J, Yang, Z, Ge, XY, et al. (2022) Autonomous sensing of the insulin peptide by an olfactory G protein-coupled receptor modulates glucose metabolism. Cell Metab 34, 240–255.e210.CrossRefGoogle ScholarPubMed
Cinti, S, Mitchell, G, Barbatelli, G, et al. (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46, 2347–2355.CrossRefGoogle ScholarPubMed
Peng, Y, French, BA, Tillman, B, et al. (2014) The inflammasome in alcoholic hepatitis: its relationship with Mallory–Denk body formation. Exp Mol Pathol 97, 305–313.CrossRefGoogle ScholarPubMed
Szabo, G & Petrasek, J (2015) Inflammasome activation and function in liver disease. Nat Rev Gastroenterol Hepatol 12, 387–400.CrossRefGoogle ScholarPubMed
Mandrekar, P & Szabo, G (2009) Signalling pathways in alcohol-induced liver inflammation. J Hepatol 50, 1258–1266.CrossRefGoogle ScholarPubMed
Kayagaki, N, Wong, MT, Stowe, IB, et al. (2013) Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science 341, 1246–1249.CrossRefGoogle ScholarPubMed
Rossi, JL, Velentza, AV, Steinhorn, DM, et al. (2007). MLCK210 gene knockout or kinase inhibition preserves lung function following endotoxin-induced lung injury in mice. Am J Physiol Lung Cell Mol Physiol 292, L1327–L1334.CrossRefGoogle ScholarPubMed
Iborra, FJ, Jackson, DA & Cook, PR (2001) Coupled transcription and translation within nuclei of mammalian cells. Science 293, 1139–1142.CrossRefGoogle ScholarPubMed
Galli-Taliadoros, LA, Sedgwick, JD, Wood, SA, et al. (1995) Gene knock-out technology: a methodological overview for the interested novice. J Immunol Methods 181, 1–15.CrossRefGoogle ScholarPubMed
Ogiyama, T, Yamaguchi, M, Kurikawa, N, et al. (2017) Identification of a novel hormone sensitive lipase inhibitor with a reduced potential of reactive metabolites formation. Bioorgan Med Chem 25, 2234–2243.CrossRefGoogle ScholarPubMed
Li, LY, Wang, Y, Limbu, SM, Li, JM, et al. (2021) Reduced fatty acid β-oxidation improves glucose catabolism and liver health in Nile tilapia (Oreochromis niloticus) juveniles fed a high-starch diet. Aquaculture 535, 736392.CrossRefGoogle Scholar
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